Alprazolam formulations

Abstract

Alprazolam is a drug used to treat anxiety disorders. Disclosed are sustained-release and controlled-release formulations containing alprazolam. The dosage forms may have particular dissolution profiles and plasma concentrations. Preferred dosage forms do not contain hydroxypropyl methylcellulose.

1 . A sustained-release dosage form comprising 
 alprazolam or a pharmaceutically acceptable salt thereof,    and a release-retarding material, wherein the release-retarding material does not comprise hydroxpropyl methylcellulose.    
     
     
         2 . The dosage form of  claim 1 , wherein the release-retarding material is an acrylate polymer, shellae, zein, hydrogenated vegetable oil, hydrogenated castor oil, or a combination comprising one or more of the foregoing release-retarding materials.  
     
     
         3 . (canceled)  
     
     
         4 . The dosage form of  claim 1 , exhibiting a dissolution profile such that at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.  
     
     
         5 . The dosage form or  claim 4 , wherein the dissolution medium has a pH of about 6.8.  
     
     
         6 . The dosage form of  claim 5 , wherein dissolution is measured by a disintegration test of the Japanese Pharmacopoeia Volume 14, 2001, Pages 31-33, performed in a second fluid.  
     
     
         7 . The dosage form of  claim 1 , exhibiting a dissolution profile such that at 9 hours after combining the dosage form with a dissolution medium, greater than 75 wt % and less than 95 wt % or the alprazolam or the pharmaceutically acceptable salt thereof is released.  
     
     
         8 . The dosage form of  claim 7 , wherein the dissolution medium has a pH of about 6.8.  
     
     
         9 . (canceled)  
     
     
         10 . The dosage form of  claim 1 , exhibiting a dissolution profile such that 
 at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released;    at 4.5 hours after combining the dosage form with the dissolution medium, greater than 25 wt % to less than 50 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released; and    at 9 hours after combining the dosage form with the dissolution medium, less than 75 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.    
     
     
         11 . The dosage form of  claim 10 , wherein the dissolution medium has a pH of about 6.8.  
     
     
         12 . (canceled)  
     
     
         13 . The dosage form of  claim 1 , exhibiting a dissolution profile such that 
 at 2 hours after combining the dosage form with a dissolution medium, greater than 25 wt %, of the alprazolam or the pharmaceutically acceptable salt thereof is released;    at 4.5 hours after combining the dosage form with the dissolution medium, greater than 50 wt % to loss than 75 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released; and    at 9 hours after combining the dosage form with the dissolution medium, greater than 75 wt % to less than 95 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.    
     
     
         14 . The dosage form of  claim 13 , wherein the dissolution medium has a pH of about 6.8.  
     
     
         15 . The dosage form of  claim 13 , wherein dissolution is measured by a disintegration test of the Japanese Pharmacopoeia Volume 14, 2001, Pages 31-33, performed in a second fluid.  
     
     
         16 . A dosage form comprising alprazolam or a pharmaceutically acceptable salt thereof, and a release-retarding material, exhibiting a dissolution profile such that at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.  
     
     
         17 . The dosage form of  claim 16 , wherein the release-retarding material does not comprise hydroxypropyl methylcellulose.  
     
     
         18 . The dosage form of  claim 16 , exhibiting a dissolution profile such that 
 at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released;    at 4.5 hours after combining the dosage form with the dissolution medium, greater than 25 wt % to less than 50 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released; and    at 9 hours after combining the dosage form with the dissolution medium, less than 75 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.    
     
     
         19 . The dosage form of  claim 16 , wherein the dissolution medium has a pH of about 6.8.  
     
     
         20 . The dosage form of  claim 16 , wherein the dissolution is measured by a disintegration test of the Japanese Pharmacopocia Volume 14, 2001, Pages 31-33, performed in a second fluid.  
     
     
         21 - 25 . (canceled)  
     
     
         26 . An oral dosage form comprising alprazolam or a pharmaceutically acceptable salt thereof in controlled-release form which provides a maximum alprazolam plasma concentration (C max ) and an alprazolam plasma concentration at about 24 hours after administration (C 24 ), wherein a ratio of C max  to C 24  is less than about 4:1.  
     
     
         27 . The oral dosage form of  claim 26 , wherein the ratio of C max  to C 24  is achieved at steady-state.  
     
     
         28 . The oral dosage form of  claim 26 , wherein the ratio of C max  to C 24  is less than about 2:1.  
     
     
         29 - 44 . (canceled)